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Background Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved. Methods Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4 weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7 weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing. Results Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota. Conclusions A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development. Graphical Abstract

Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterized by diffuse fibrosis of the skin and internal organs and vascular abnormalities. The etiology and physiopathology are complex due to the heterogeneity of its overall clinical presentation. Arsenic trioxide (ATO) has been proven to be effective against SSc, sclerodermatous Graft-versus-Host Disease, multiple sclerosis, Crohn's disease or systemic lupus erythematosus animal models and has demonstrated promising effects in human clinical trials. Its efficacy was shown to be related at least in part to the generation of Reactive Oxygen Species (ROS) and the selective deletion of activated immune cells and fibroblasts. However, ATO can induce some adverse effects that must be considered, especially when used for the treatment of a chronic disease. We evaluate here, and in a mouse model of SSc, the improved efficacy of ATO when associated with a Fenton-like divalent cation, namely copper chloride (CuCl ), also known to trigger the production of ROS. In preliminary experiments , ATO 1 µM + CuCl 0.5 µM increased ROS production and increased apoptosis of NIH 3T3 murine fibroblasts compared to 1 µM ATO alone. , in the HOCl-induced mouse model of SSc, co-treatment with ATO 2.5 μg/g + CuCl 0.5 μg/g significantly alleviated clinical signs such as the thickening of the skin (p<0.01) and cutaneous fibrosis, in a manner equivalent to treatment with ATO 5 µg/g. Our results provide evidence that co-treatment with ATO 2.5 μg/g + CuCl 0.5 μg/g decreases the number of B cells and the activation of CD4 T lymphocytes. The co-treatment substantially blocks the NRF2 signaling pathway, increases H2O2 production and results in the improvement of the health status of mice with experimental SSc. In conclusion, copper combined with ATO treatment halved the concentration of ATO needed to obtain the same effect as a high dose of ATO alone for the treatment of SSc mice. The strategy of using lower doses of drugs with different mechanisms of action in combination has many potential advantages, the first being to lessen the potential side effects induced by ATO, a drug with side effects quickly increased with dosage.

Widespread global declines in shellfish reefs (ecosystem‐forming bivalves such as oysters and mussels) have led to growing interest in their restoration and protection. With restoration projects now occurring on four continents and in at least seven countries, global restoration guidelines for these ecosystems have been developed based on experience over the past two decades. The following key elements of the guidelines are outlined: (a) the case for shellfish reef restoration and securing financial resources; (b) planning, feasibility, and goal setting; (c) biosecurity and permitting; (d) restoration in practice; (e) scaling up from pilot to larger scale restoration, (f) monitoring, (g) restoration beyond oyster reefs (specifically mussels), and (h) successful communication for shellfish reef restoration projects.

Despite significant therapeutic advances, graft- versus -host disease (GvHD) remains the main life-threatening complication following allogeneic hematopoietic stem cell transplantation. The pathogenesis of GvHD is dominated by a dysregulated allogeneic immune response that drives fibrosis and autoimmunity in chronic forms. A multitude of cell therapy approaches, including infusion of myeloid cells, has been proposed to prevent GvHD through tolerance induction but yielded variable results. Myeloid cells like macrophages can be reprogrammed to develop adaptive-like features following antigenic challenge to reinforce or inhibit a subsequent immune response; a phenomenon termed ‘trained immunity’. Here we report that, whereas LPS low -trained macrophages elicit a suppressor effect on allogeneic T cell proliferation and function in vitro in an IL-10-dependent manner, Bacille Calmette et Guérin (BCG)-trained macrophages exert an opposite effect. In a murine model of sclerodermatous chronic GvHD, LPS low -trained macrophages attenuate clinical signs of GvHD with significant effects on T cell phenotype and function, autoantibodies production, and tissue fibrosis. Furthermore, infusion of LPS low -macrophages significantly improves survival in mice with acute GvHD. Importantly, we also provide evidence that LPS low -macrophages do not accelerate A20-lymphoma tumor growth, which is significantly reduced upon transfer of BCG-macrophages. Collectively, these data indicate that macrophages can be trained to significantly inhibit in vitro and in vivo allo-reactive T cell proliferation without exhibiting pro-tumoral effect, thereby opening the way to promising clinical applications.

Graft-versus Host Disease (GvHD) is a major complication of hematopoietic stem cell transplant. GvHD is characterized by the chronic activation of immune cells leading to the development of systemic inflammation, autoimmunity, fibrosis and eventually death. Arsenic trioxide (ATO) is a therapeutic agent under clinical trial for the treatment of patients with systemic lupus erythematosus (SLE) and chronic GvHD (cGvHD). This therapy is admittedly rather safe although adverse effects can occur and may necessitate short interruptions of the treatment. The aim of this study was to combine ATO with a divalent cation, to generate a Fenton or Fenton-like reaction in order to potentiate the deletion of activated immune cells through the reactive oxygen species (ROS)-mediated effects of ATO in a mouse model, and thereby enabling the use of lower and safer ATO concentrations to treat patients with cGvHD. In vitro , among the various combinations of divalent cations tested, we observed that the combination of ATO and CuCl 2 (copper chloride) induced a high level of oxidative stress in HL-60 and A20 cells. In addition, this co-treatment also decreased the proliferation of CD4 + T lymphocytes during a mixed lymphocyte reaction (MLR). In vivo , in a cGvHD mouse model, daily injections of ATO 2.5 µg/g + CuCl 2 0.5 µg/g induce a decrease in lymphocyte activation and fibrosis that was equivalent to that induced by ATO 5 µg/g. Our results show that the addition of CuCl 2 improved the effects of ATO and significantly limited the development of the disease. This co-treatment could be a real benefit in human patients to substantially decrease the known ATO side effects and optimize ATO treatment in pathologies characterized by activated cells sensitive to an increase in oxidative stress.

Delivering both social and ecological outcomes is regarded as essential for conservation actions to be effective, particularly in regions where Indigenous Peoples (IPs) and local communities (LCs) depend heavily on natural resources. In the Indo‐Pacific, sustainable small‐scale fisheries are seen as potential win–win solutions. Here, we evaluate the opportunities and challenges of supporting IPs and LCs to sustainably manage and add value to a high‐value marine commodity using a case study from the Mwanus Endras Asi Resource Development Network (MEARDN) in Manus Province, Papua New Guinea. Between 2017 and 2018, MEARDN, with support from The Nature Conservancy, implemented management measures exceeding national requirements and exported beche‐de‐mer that had obtained sustainable certification directly to Hong Kong. While initially successful, this initiative struggled to remain viable amid rapidly shifting governance, market, cultural, and social dynamics. Our findings highlight the challenges of delivering conservation and sustainable livelihoods where natural resource systems are subject to intense economic pressures.

Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline ( ex vivo ). After stimulation (assessed through plate-bound antibodies against activating receptors or culture in the presence of cytokines such as interleukin (IL)-2 or IL-15) however, they can become cytotoxic and produce cytokines. This is particularly the case in transporter associated with antigen processing (TAP)-deficient mice, which we investigated in the present study. Transporter associated with antigen processing transports endogenous peptides from the cytosol to the endoplasmic reticulum, where they are loaded on nascent MHC class I molecules, which then become stable and expressed at the cell surface. Consequently, TAP-KO mice have very low levels of MHC class I expression. We present a study about phenotypic and functional aspects of NK cells in two mouse strains, C57BL/6 wildtype and TAP1-KO in spleen and lung. We observed that in both types of mice, on the same genetic background, the initial pattern of education, conferred to the cells via the inhibitory receptors Ly49C/I and NKG2A, was maintained even after a strong stimulation by the cytokines interleukin-2, interleukin-12, interleukin-15 and interleukin-18. Furthermore, the percentages of activated NK cells expressing Ly49C/I and Ly49I were strongly down-modulated under these conditions. We completed our investigations with phenotypic studies of NK cells from these mice.

Reactive oxygen species (ROS) are produced by every aerobic cell during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Superoxide Dismutases (SOD) are antioxidant proteins that convert superoxide anions (O2•−) to hydrogen peroxide (H2O2) and dioxygen. Using the differential in the level of oxidative stress between normal and cancer cells, SOD mimetics can show an antitumoral effect and prevent oxaliplatin-induced peripheral neuropathy. New Pt(IV) conjugate prodrugs (OxPt-x-Mn1C1A (x = 1, 1-OH, 2)), combining oxaliplatin and a Mn SOD mimic (MnSODm Mn1C1A) with a covalent link, were designed. Their stability in buffer and in the presence of sodium ascorbate was studied. In vitro, their antitumoral activity was assessed by the viability and ROS production of tumor cell lines (CT16, HCT 116, KC) and fibroblasts (primary culture and NIH 3T3). In vivo, a murine model of colorectal cancer was created with subcutaneous injection of CT26 cells in Balb/c mice. Tumor size and volume were measured weekly in four groups: vehicle, oxaliplatin, and oxaliplatin associated with MnSODm Mn1C1A and the bis-conjugate OxPt-2-Mn1C1A. Oxaliplatin-induced peripheral neuropathy (OIPN) was assessed using a Von Frey test reflecting chronic hypoalgesia. Tolerance to treatment was assessed with a clinical score including four items: weight loss, weariness, alopecia, and diarrhea. In vitro, Mn1C1A associated with oxaliplatin and Pt(IV) conjugates treatment induced significantly higher production of H2O2 in all cell lines and showed a significant improvement of the antitumoral efficacy compared to oxaliplatin alone. In vivo, the association of Mn1C1A to oxaliplatin did not decrease its antitumoral activity, while OxPt-2-Mn1C1A had lower antitumoral activity than oxaliplatin alone. Mn1C1A associated with oxaliplatin significantly decreased OIPN and also improved global clinical tolerance of oxaliplatin. A neuroprotective effect was observed, associated with a significantly improved tolerance to oxaliplatin without impairing its antitumoral activity.

Oyster reefs are structurally complex habitats which are increasingly recognized for their importance in estuarine systems. With over 85% of oyster reefs lost to human activities globally, there is increasing interest in aquaculture to not only meet the growing need for food worldwide, but also enhance ecological functions and services. Prime among these services is the provision of habitat for marine biodiversity. We assessed the biodiversity associated with an abandoned benthic oyster farm to investigate the potential ecological benefits of benthic farming techniques used in traditional oyster farms. In addition, we made note of any invasive species which may use these abandoned structures as habitat. The macrobenthic assemblage in the oyster habitat formed by the farm was different from the surrounding mudflats, containing 61 and 26 species, respectively. Density of invertebrates was similar in both habitats (~ 5,777 ± 981 indiv·m −2 ), but biomass in the oyster farm over ten times greater than the mudflat substrate, which had a fauna dominated by small polychaetes (<5 mm long). Molluscs and crustaceans were especially abundant in the oyster habitat and contributed to 90% of the enhanced biomass associated with oyster habitat (excluding oyster biomass). Only one invasive species was documented, the mussel Xenostrobus secures , but at densities lower than nearby artificial substrates (e.g., concrete shorelines). Oyster development on this abandoned farm appears to be self-sustaining, provide habitat and trophic support for associated benthic macrofauna. In addition to supporting higher biodiversity and biomass of associated species, traditional oyster aquaculture could improve the restoration potential of oyster reefs by supporting broodstock of native oysters, thus maintaining larval supply.

After traumatic brain injury (TBI), the relationship between age and outcome at 1 year, including quality of life, has been poorly explored. The aim of our study was to describe this relationship in a cohort of TBI patients in a regional trauma system. Consecutive TBI patients with severe lesions on initial brain computed tomography (CT) scan were included from July 2014 to July 2016 in two French level-1 trauma centers. The primary outcome was the mortality at 1 year and secondary outcomes were Glasgow Outcome Scale-Extended (GOS-E) and quality of life using the Short Form Health Survey (SF-12). The relationship between age and outcome was modeled using the generalized linear model (GLM). Within the study period, 427 patients with TBI and type 3 Abbreviated Injury Scale (AIS) lesions were included. Finally, 380 patients were assessed for mortality. Ninety-six (25%) patients died at 1 year. The detailed neurological status was available for 317 patients. One year after the trauma, 141 (44%) patients had a favorable outcome (GOS-E 7 and 8), whereas 53 (17%) patients had a moderate disability (GOS-E 5–6), 27 (9%) patients had a severe disability or were in a vegetative state (GOS-E 2–4), and 96 (30%) patients had died (GOS-E 1). After 70 years of age, a dramatic increase in the odds of death and poor neurological outcome was found using GLM. No difference according to age was found for the quality of life. After TBI, the mortality at 1 year dramatically increased with age after 70 years. For elderly survivors, impairment of quality of life was not different from younger patients.